The present invention is directed to an improved process for the production of methyl and ethyl esters of cyclopropane carboxylic acids, by, in a given case continuously, cyclizing .gamma.-chlorocarboxylic acid methyl and ethyl esters (i.e. methyl and ethyl esters of .gamma.-chloroalkanoic acids) in the presence of an alcoholate and an alcohol at elevated temperature.
Esters of cyclopropane carboxylic acids are valuable intermediate products for the production of agrochemicals, especially insecticides, and pharmaceutical chemicals.
It is known to condense the ethyl ester of 4-chlorobutyric acid with aqueous potassium hydroxide on pumice. There is obtained thereby in moderate yield the ethyl ester of cyclopropane carboxylic acid besides the free acid and .gamma.-butyrolactone (Rambaud, BL. [5] (1938), pages 1552, 1564).
It is also known to cyclize esters using water free alcoholates. For example the ethyl ester of .gamma.-chlorobutyric acid is boiled under refluxed with sodium t-amylate in t-amyl alcohol for four hours. There is obtained the ethyl ester of cyclopropane carboxylic acid in a yield of 45% of theory. If there is used sodium diemthyl benzylate as the condensing agent the yield is 47% of theory. (Julia et al, Bull. Soc. Chimie (France) 1960, pages 306 et seq.).
Furthermore it is known that the cyclization can take place in inert solvents. For example there is described the cyclization of 5-methyl-3-(1-chloroisopropyl)-hex-4-enoate with sodium-t-amylate in benzene to dl-transchrysanthemunic acid methyl ester. The yield is 41.8% respectively 53.6% (Julia U.S. Pat. No. 3,077,496, Julia U.S. Pat. No. 3,123,629).
In Phillips U.S. Pat. No. 3,711,549 for the claimed process for the production of aqueous cyclopropylamine in the first step of the process there is formed the reaction of methyl-4-chloro-butyrate with sodium methylate in an inert gas atmosphere in a non-reactive organic liquid under moisture free conditions. The yield of methyl cyclopropanecarboxylate is 92% of theory.
It is also known to condense .gamma.-chlorocaproic acid ester with sodamide in ether for 4 to 5 days and thereby to 2-methylcyclopropanecarboxylic acid esters in a yield of 85% of theory. A similar experiment with .alpha.-methyl-.gamma.-chlorbutyric acid ethyl ester gives 1-methylcyclopropanecarboxylic acid ethyl ester in a yield of 47.6% (Cannon J. Amer. Chem. Soc. Vol. 81, pages 1660-1666). This same article similarly shows the preparation of ethyl 1,2,2-trimethylcyclopropane-1-carboxylate in a yield of 71.5%.
In Japanese patent application No. J 749-28509 there is described the condensation of .gamma.-chlorobutyric acid ethyl ester with NaH in paraffin. There is obtained ethyl cyclopropanecarboxylate in a yield of 87.9% of theory.
There has further been described the cyclization of 6-bromo-2,3,3-trimethyl-4-hexenoic acid ethyl ester with potassium-t-butoxide in water free tetrahydrofurane to 1-methyl-2-vinyl-3,3-dimethylcyclopropanecarboxylic acid ethyl ester. The yield is 55% of theory (Japanese patent application No. 51-82242).
Bunce et al in "Organic Preparations and Procedures INc.", 6, pages 193-6 (1974) describe the production of ethyl cyclopropanecarboxylate from .gamma.-chlorobutyric acid ethyl ester and sodium ethylate in ethanol. The yield is 66% of theory. G. M. Lampman et al (I. Chem. Eng. Data 14, page 396 (1969)) describe the production of ethyl cyclopropane carboxylate from 4-bromobutyric acid ethyl ester by cyclization with NaH. The yield is 88% of theory.
All of these known processes show that industrially interesting yields can be attained if there is used as the condensation agent sodium hydride, sodamide or alcohol free alcoholate and the process is operated in the absence of non-inert solvents or dispersing agents. If for example the alcoholate in alcohol is used, there occurs a sharp reduction in yield.
In the case of the cyclization of the ethyl ester of .gamma.-chlorobutyric acid with sodium ethylate in ethanol, besides the cyclopropanecarboxylic acid cyclization another reaction proceeds, namely the formation of the 4-ethoxybutyric acid ethyl ester. Furthermore there must be considered recyclizing in the direction of butyrolactone. This explains the poor yield of 66% of theory. This is also true for the methyl ester.
The use of sodium hydride or sodamide is dangerous and expensive. A carrying out of this cyclization process on an industrial scale is very difficult.
Water free (anhydrous) alcoholates likewise are expensive, their handling is very expensive and requires a large industrial expenditure. Dusts of sodium or potassium methylate or ethylate are injurious to health and have a strongly corrosive action. Water free alcoholates hydrolyze easily, thereby the free bases are formed which disturb the cyclization process, since they saponify the starting compounds (esters). If there is used for example sodium methylate in toluene for the cyclization of .gamma.-chlorobutyric acid methyl ester according to Phillips U.S. Pat. No. 3,711,549 on an industrial scale, there is obtained in this process the most finely divided sodium chloride which adheres to the walls of the reactor and as a result considerably disturbs the heat transfer. The result is that in the industrial synthesis there must frequently be used a large excess alkali alcoholate. If condensation is carried out according to this process there is obtained sodium or potassium chloride or bromide in the most finely divided state which immediately encases the sodium or potassium alcoholate so that only a portion of the condensation agent employed is effective. This condition can be partially eliminated if the reaction medium is kept in strong motion and the reaction time increased sharply. In any case additional technical requirement must be used in the process disclosed in the above patent to permit industrial realization thereof.